Non-halogenated phenoxy and/or benzyloxy substituted phenols, antimicrobial compositions containing the same, and methods of using the same

ABSTRACT

Antimicrobial compounds, compositions containing the same, and methods of using of the same for reducing the presence of microorganisms on a substrate or in a fluid environment comprising an antimicrobial effective carrier and at least one antimicrobial compounds including non-halogenated phenoxy and/or benzyloxy substituted phenol compounds.

[0001] This continuation application claims the benefit of U.S. patentapplication Ser. No. 10/026,990, Filed Dec. 20, 2001, which claims thebenefit of U.S. Provisional Patent Application No. 60/256,789, filed onDec. 20, 2000, the entirety of which is hereby incorporated by referenceas if fully set forth herein.

FIELD OF THE INVENTION

[0002] The present invention relates to antimicrobial compounds andcompositions containing such compounds, and more particularly to phenoxyand/or benzyloxy substituted phenol compounds exhibiting antimicrobialactivity, antimicrobial compositions containing phenoxy and benzyloxysubstituted phenol compounds, and methods of using such compositions.

BACKGROUND OF THE INVENTION

[0003] Recently, attention has focused on personal hygiene in light ofmounting concerns about public health. There is a growing awareness ofvarious microorganisms and microbial pathogens such as yeast, fungi,bacteria, molds and viruses, that can cause disease upon access andentry into the body such as through the eyes, ears, nose, mouth andskin. These microbes are generally transmitted from a source (e.g. acontaminated surface) by the hands to a person's body. Thus, a number ofillnesses may easily be prevented by decontamination of the skin and thehands. In a related vein, the control of pathogenic or otherwiseundesirable microbes is also a concern in promoting good oral hygiene,where reducing populations of microorganisms on the teeth, gums andtongue has been shown useful in controlling dental plaque accumulation,gingivitis, oral malodor, and other oral maladies.

[0004] It has been shown that at least 18 percent of the population isafflicted with some form of a microbial infection of the dermis.Although such infections are more common in third world areas, there isalso a substantial incidence of the infections in developed areas wherea high level of personal hygiene exists. Studies have further shown thatthe factors that contribute to rising incidence of such infectionsinclude longer lifespans, emerging resistance of microbes toantibiotics, increased use of antineoplastic agents, and a growingpopulation of patients with some deterioration in their immune system.

[0005] Microbial infections and disease are caused by many types ofmicroorganisms. Most infections are typically the result of microbialinfection and/or the presence of microorganisms such as on the skin ofthe hand or foot, for example. Accordingly, it has been noted thateffective treatments of such infections should also include properpreventive measures, specifically, thorough sanitization of the skinincluding the hands and contact surfaces to prevent furthercontamination and/or transmission to other individuals.

[0006] Treatment of infection typically includes the application oftopical or systemic antibiotic/antifungal agents. Such therapies aredisadvantageous because they exhibit a limited rate of success, arecontraindicated and/or have undesirable drug interactions, produceelevated levels of toxicity, and/or are expensive. Additionally, thescientific and medical communities have moved away from the use of suchsystemic antimicrobial therapy for oral and general infection controldue to an increase in the number of resistant strains of pathogenicmicrobes.

[0007] Antimicrobial cleansing compositions for use on the hands, skin,and scalp have used a variety of antimicrobial ingredients includinganionic surface-active agent (e.g. sodium lauryl sulfate), coal tar,cationic antimicrobial agents such as chlorhexidine, and halogenatednonionic antimicrobial agents such as triclosan and hexachlorophene.

[0008] In addition to being present external to the body, microorganismsare also present in the oral cavity. Among undesirable microorganismsare Gram-positive and Gram-negative bacterial species associated withthe formation of dental plaque (a dense, enamel-adherent biofilmconsisting of microorganisms and their attendant extracellular matrix).Dental plaque is initially soft and removable by mechanical oralhygiene, but can undergo mineralization to form hard deposits of dentalcalculus. Although dental plaque may form on any part of the toothsurface, accumulation of plaque at the gingival margin is particularlyimplicated in the occurrence of gingivitis. Even with good oral hygiene,it has been shown that microorganisms (include those responsible forplaque formation) rapidly multiply and build up in the oral cavity, andmany individuals have difficulty in maintaining good plaque control withbrushing and flossing alone.

[0009] Specific areas, including periodontal and subgingival spaces, aswell as interpapillary spaces of the tongue and tonsils provide afavorable environment for harboring bacteria and other microbes. Quiteoften the use of dentifrices such as toothpaste, and/or toothbrushes,dental flosses, and cosmetic mouthrinses, is insufficient to control theundesirable microorganisms. The persistence of these microorganisms insuch environments greatly increases the risk of plaque and calculusbuild-up, which in turn presents a danger of gingival inflammation andmore advanced forms of periodontal disease. In addition, the productionof malodorous volatile compounds by accumulated populations of anaerobicmicroorganisms in dental plaque or on the tongue dorsum may lead toperceptible oral malodor.

[0010] Accordingly, it is highly desirable to include antimicrobial(antibacterial) agents in topical or oral compositions having biocidaland/or biostatic activity against a variety of microorganisms.Microorganisms of concern in hand and skin care include Gram-negativebacteria such as Escherichia coli and Pseudomonas aeruginosa, Grampositive bacteria such as Staphylococcus aureus and Propionibacteriumacnes, molds such as Aspergillus niger and Penicillium funiculosum,yeasts such as Candida albicans, Saccharomyces cerevisiae andPityrosporum ovale, dermatophytic fungi such as Trichophyton rubrum,microalgae such as Chlorella spp. and Spyrogyra spp., and viruses suchas Herpes virus and Picornavirus. Microorganisms of concern in dentalplaque, gingivitis, malodor and other oral maladies in the oral cavityinclude Fusobacterium nucleatum, Prevotella intermedia, Actinomycesviscosus, Streptococcus sanguis, Streptococcus mutans, and Candidaalbicans.

[0011] One type of oral composition used as a standard in oral hygieneis mouthrinse. However, many mouthrinses have only been effective inmasking halitosis. These include mouthrinses which comprise quaternaryamines (e.g., combinations of ethanol and domiphen bromide and/orcetylpyridinium chloride) or mixtures of orally acceptablesurface-active agents or surfactants. Several mouthrinses that have beenmarketed for the reduction of plaque and gingivitis generally rely oncationic agents such as chlorhexidine digluconate, metallic fluoridesalts such as stannous fluoride, antimicrobial essential oils (e.g.,thymol, eucalyptol, ethanol, menthol and methyl salicylate), and/orwater-insoluble phenolic agents such as triclosan.

[0012] The cationic antimicrobial materials such as chlorhexidine,benzethonium chloride, and cetyl pyridinium chloride have beeninvestigated as antimicrobial agents for the control of gingivitisand/or oral malodor. The antimicrobial activity of these materials istheorized to be linked to the cationic charge(s) of the molecule. Thischarge is attracted to negatively-charged moieties on the cell membraneor wall of the microorganism, and facilitates attachment to the surfaceof the microorganism. The attachment and subsequent interaction with thecell surface disrupts the cell membrane structure, causing leakage ofthe intracellular fluids, eventually killing the microorganism. However,such materials are generally not effective when formulated incombination with anionic materials and when other cationic minerals andorganic molecules present in hard water which may interfere withattraction and subsequent attachment of the cationic materials to thenegatively-charged moieties. These chemical interactions may therebyreduce the overall antimicrobial efficacy of this class of compounds.Noncationic antimicrobial materials, on the other hand can be compatiblewith anionic components of an oral antimicrobial composition or othertype of compositions containing an antimicrobial agent.

[0013] Halogenated hydroxydiphenyl ethers such as triclosan have beeneffectively employed in oral compositions as antimicrobial agents.However, halogenated compounds may present safety issues.

[0014] Alternatives to triclosan with similar antimicrobial activityhave been the subject of continuing investigation. Alkyl substitutedphenols, such as thymol (2-isopropyl-5-methyl phenol), are well knownand widely used as antimicrobials. In combination with menthol,eucalyptol, and methyl salicylate, thymol is an active antimicrobialagent, for example, in commercial clinically effectiveanti-plaque/anti-gingivitis mouthrinse formulations. However, suchessential oil formulations possess lower antimicrobial potency thanthose containing triclosan. Non-halogenated alternatives to triclosanwith similar or improved antimicrobial activity have been the subject ofinventors□ investigation.

[0015] Accordingly, it would be a significant advance in the art ofpersonal and dental hygiene to provide new non-halogenated antimicrobialcompounds and compositions containing such compounds which exhibitsubstantial antimicrobial effectiveness and yet do not possess thesafety concerns often associated with halogenated compounds such astriclosan.

SUMMARY OF THE INVENTION

[0016] In accordance with the present invention, phenoxy and/orbenzyloxy substituted phenol compounds exhibiting effectiveantimicrobial activity are disclosed. In one aspect of the invention,phenoxy substituted phenol compounds are disclosed of Formula (1):

[0017] wherein

[0018] R₁ is selected from the group

[0019] R₂ and R₃ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkylgroup; an alkyl group substituted with phenyl in which phenyl isoptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group; phenyl optionally substituted with a memberselected from the group consisting of an alkyl group, a cycloalkylgroup, a hydroxyalkyl group, and a hydroxycycloalkyl group; and benzyloptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group;

[0020] R₄ is selected from the group consisting of hydrogen, an alkylgroup, a cycloalkyl group, benzyl, and phenyl;

[0021] R₅ is selected from the group consisting of hydroxyl, benzyl,alkoxy, hydroxyalkyl, and cycloalkyl optionally substituted withhydroxyl; and

[0022] R₆ and R₇ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; benzyl, an alkoxy group; phenyl optionallysubstituted with an alkyl group, a cycloalkyl group, an alkenyl group, acycloalkenyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;an alkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenoxy; and benzyloxy;

[0023] with the proviso that:

[0024] a) when R₁ is a

[0025]  and R₂ and R₄ are each hydrogen, and

[0026] 1) when R₃ is hydrogen, then R₆ is not hydrogen, methyl,tert-butyl, phenyl, or phenoxy;

[0027] 2) when R₅ is hydroxyl and one of R₃ and R₆ is hydrogen, then theother ot R₃ and R₆ is not selected from the group consisting ofhydrogen, n-propyl, n-butyl, n-pentyl, 1-methylethyl, 2-methylpropyl,3-methylbutyl, benzyl, or cyclohexyl;

[0028] 3) when R₃ and R₆ are each hydrogen, then R₅ is not benzyl;

[0029] 4) when R₅ is hydroxyl and R₃ is ethyl, then R₆ is not methyl;

[0030] 5) when R₅ is hydroxyl and R₃ is tert-butyl, then R₆ is nottert-butyl;

[0031] b) when R₁ is a

[0032]  R₃, R₄ and R₆ are each hydrogen, and R₅ is hydroxyl, then R₂ isnot selected from the group consisting of phenyl and tert-butyl;

[0033] c) when R₁ is a

[0034]  R₅ is hydroxyl, and R₆ is hydrogen, then none of R₂, R₃, and R₄is C₁-C₄ alkyl, the other two of R₂, R₃, and R₄ being hydrogen;

[0035] d) when R₁ is a and each of R₂, R₃ is hydrogen, and

[0036] 1) when R₄ is hydrogen, then R₇ is not selected from the groupconsisting of 4-methyl and 4-methoxy;

[0037] 2) when R₄ is tert-butyl, then R₇ is not hydrogen;

[0038] 3) at least one of R₁, R₂, R₃, and R₄ is not hydrogen.

[0039] In another aspect of the present invention, an antimicrobialcomposition comprising an effective amount of at least one antimicrobialcompound including phenoxy and/or benzyloxy substituted phenol compoundsfor reducing the presence of microorganisms on a substrate or in a fluidenvironment in combination with an antimicrobial effective carrier. Insuch aspect of the invention, there is provided an antimicrobialcomposition comprising an antimicrobial effective amount of at least oneantimicrobial compound of Formula (II):

[0040] wherein

[0041] R₁ is selected from the group

[0042] R₂ and R₃ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkylgroup; an alkyl group substituted with phenyl in which phenyl isoptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group; phenyl optionally substituted with a memberselected from the group consisting of an alkyl group, a cycloalkylgroup, a hydroxyalkyl group, and a hydroxycycloalkyl group; and benzyloptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group;

[0043] R₄ is selected from the group consisting of hydrogen, an alkylgroup, a cycloalkyl group, benzyl, and phenyl;

[0044] R₅ is selected from the group consisting of hydroxyl, benzyl,alkoxy, hydroxyalkyl, and cycloalkyl optionally substituted withhydroxyl; and

[0045] R₆ and R₇ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; benzyl, an alkoxy group; phenyl optionallysubstituted with an alkyl group, a cycloalkyl group, an alkenyl group, acycloalkenyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;an alkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenoxy; and benzyloxy;

[0046] with the proviso that:

[0047] a) when R₁ is

[0048]  and R₂ and R₄ are each hydrogen, and

[0049] 1) when R₃ is hydrogen, then R₆ is not hydrogen or methyl;

[0050] 2) when R₃ is hydrogen and R₅ is hydroxyl, then R₆ is nothydrogen;

[0051] 3) when R₃ is tert-butyl and R₅ is hydroxyl, then R₆ is not4-tert-butyl;

[0052] b) when R₁ is

[0053]  then none of R₂, R₃ and R₄ is C₁-C₄ alkyl, the other two of R₂,R₃ and R₄ being hydrogen; and

[0054] an antimicrobial effective carrier.

[0055] In another aspect of the invention there is provided an oralantimicrobial composition comprising an effective antimicrobial amountof at least one antimicrobial compound including phenoxy and/orbenzyloxy substituted phenol compounds for reducing the presence ofmicroorganisms in an oral cavity in combination with an orallyacceptable carrier.

[0056] In this aspect of the present invention, an oral compositioncomprises an antimicrobial effective amount of at least oneantimicrobial compound of Formula (III):

[0057] wherein

[0058] R₁ is selected from the group

[0059] R₂ and R₃ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkylgroup; an alkyl group substituted with phenyl in which phenyl isoptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group; phenyl optionally substituted with a memberselected from the group consisting of an alkyl group, a cycloalkylgroup, a hydroxyalkyl group, and a hydroxycycloalkyl group; and benzyloptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group;

[0060] R₄ is selected from the group consisting of hydrogen, an alkylgroup, a cycloalkyl group, benzyl, and phenyl;

[0061] R₅ is selected from the group consisting of hydroxyl, benzyl,alkoxy, hydroxyalkyl, and cycloalkyl optionally substituted withhydroxyl; and

[0062] R₆ and R₇ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; benzyl, an alkoxy group; phenyl optionallysubstituted with an alkyl group, a cycloalkyl group, an alkenyl group, acycloalkenyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;an alkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenoxy; and benzyloxy;

[0063] with the proviso that

[0064] a) when R, is

[0065]  then each of R₂, R₃, R₄, and R₆ is not hydrogen; and

[0066] b) when R, is

[0067]  then none of R₂, R₃ and R₄ is C₁-C₄ alkyl, the other two of R₂,R₃ and R₄ being hydrogen; and

[0068] an orally acceptable carrier.

[0069] In a further aspect of the invention, methods are provided forusing the antimicrobial composition comprising at least oneantimicrobial compound of Formula (II) for reducing the presence ofmicroorganisms on a substrate. The methods include treating thesubstrate with an effective amount of the antimicrobial compositioncontaining the antimicrobial compounds of Formula (II).

[0070] In a still further aspect of the invention, methods are providedfor using the oral composition comprising at least one antimicrobialcompound of Formula (III) for reducing the presence of microorganisms inan oral cavity of an individual. The methods include administering intothe oral cavity an effective amount of the oral composition containingthe antimicrobial compounds of Formula (III).

DETAILED DESCRIPTION OF THE INVENTION

[0071] The present invention is directed to phenoxy and/or benzyloxysubstituted phenol compounds which exhibit effective antimicrobialactivities in a variety of compositions and applications whilemaintaining a positive safety profile desirable for human use. Theantimicrobial activity of the compounds of the present invention aremuch improved over those exhibited by prior art antimicrobial compounds.Since the novel compounds are composed entirely of hydrocarbonconstituents with ether linkages and hydroxyl substitutents, suchcompounds are significantly safer than prior art antimicrobial compoundssuch as halogenated phenoxyphenols or halogenateddihydroxydiphenylmethanes, for example. More specifically, the novelcompounds preferably include one or more phenoxy and/or benzyloxy groupsoptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, an alkenyl group, a hydroxyalkylgroup, and a hydroxycycloalkyl group which substantially improvesoverall antimicrobial activity for effectively reducing the presence ofmicroorganisms.

[0072] The present invention is further directed to the antimicrobialcompositions which are effective in treating various substrate surfacesincluding the oral cavity that may contain microorganisms. Theantimicrobial composition is especially effective against microorganismsresiding in the oral cavity responsible for bad breath, plaque and/orcalculus, and the resulting tooth and gum diseases that may be causedthereby. The antimicrobial composition is effective yet is safe to useand is available in a variety of forms and antimicrobial applicationsand uses.

[0073] Accordingly, the present invention provides for phenoxy and/orbenzyloxy substituted phenol compounds exhibiting antimicrobialactivities which are represented by Formula (I):

[0074] wherein

[0075] R₁ is selected from the group

[0076] R₂ and R₃ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkylgroup; an alkyl group substituted with phenyl in which phenyl isoptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group; phenyl optionally substituted with a memberselected from the group consisting of an alkyl group, a cycloalkylgroup, a hydroxyalkyl group, and a hydroxycycloalkyl group; and benzyloptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group;

[0077] R₄ is selected from the group consisting of hydrogen, an alkylgroup, a cycloalkyl group, benzyl, and phenyl;

[0078] R₅ is selected from the group consisting of hydroxyl, benzyl,alkoxy, hydroxyalkyl, and cycloalkyl optionally substituted withhydroxyl; and

[0079] R₆ and R₇ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; benzyl, an alkoxy group; phenyl optionallysubstituted with an alkyl group, a cycloalkyl group, an alkenyl group, acycloalkenyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;an alkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenoxy; and benzyloxy;

[0080] with the proviso that:

[0081] a) when R₁ is a

[0082]  and R₂ and R₄ are each hydrogen, and

[0083] 1) when R₃ is hydrogen, then R₆ is not hydrogen, methyl,tert-butyl, phenyl, or phenoxy;

[0084] 2) when R₅ is hydroxyl and one of R₃ and R₆ is hydrogen, then theother ot R₃ and R₆ is not selected from the group consisting ofhydrogen, n-propyl, n-butyl, n-pentyl, 1-methylethyl, 2-methylpropyl,3-methylbutyl, benzyl, or cyclohexyl;

[0085] 3) when R₃ and R₆ are each hydrogen, then R₅ is not benzyl;

[0086] 4) when R₅ is hydroxyl and R₃ is ethyl, then R₆ is not methyl;

[0087] 5) when R₅ is hydroxyl and R₃ is tert-butyl, then R₆ is nottert-butyl;

[0088] b) when R₁ is

[0089]  R₃, R₄ and R₆ are each hydrogen, and R₅ is hydroxyl, then R₂ isnot selected from the group consisting of phenyl and tert-butyl;

[0090] c) when R₁ is

[0091]  R₅ is hydroxyl, and R₆ is hydrogen, then none of R₂, R₃, and R₄is C₁-C₄ alkyl, the other two of R₂, R₃, and R₄ being hydrogen;

[0092] d) when R₁ is a and each of R₂, R₃ is hydrogen, and

[0093] 1) when R₄ is hydrogen, then R₇ is not selected from the groupconsisting of 4-methyl and 4-methoxy;

[0094] 2) when R₄ is tert-butyl, then R₇ is not hydrogen;

[0095] 3) at least one of R₁, R₂, R₃, and R₄ is not hydrogen.

[0096] The present invention further provides for preferred compositionscomprising an antimicrobial effective amount of at least oneantimicrobial compound of Formula (II):

[0097] wherein

[0098] R₁ is selected from the group

[0099] R₂ and R₃ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkylgroup; an alkyl group substituted with phenyl in which phenyl isoptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group; phenyl optionally substituted with a memberselected from the group consisting of an alkyl group, a cycloalkylgroup, a hydroxyalkyl group, and a hydroxycycloalkyl group; and benzyloptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group;

[0100] R₄ is selected from the group consisting of hydrogen, an alkylgroup, a cycloalkyl group, benzyl, and phenyl;

[0101] R₅ is selected from the group consisting of hydroxyl, benzyl,alkoxy, hydroxyalkyl, and cycloalkyl optionally substituted withhydroxyl; and

[0102] R₆ and R₇ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; benzyl, an alkoxy group; phenyl optionallysubstituted with an alkyl group, a cycloalkyl group, an alkenyl group, acycloalkenyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;an alkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenoxy; and benzyloxy;

[0103] with the proviso that:

[0104] a) when R₁ is

[0105]  and R₂ and R₄ are each hydrogen, and

[0106] 1) when R₃ is hydrogen, then R₆ is not hydrogen or methyl;

[0107] 2) when R₃ is hydrogen and R₅ is hydroxyl, then R₆ is nothydrogen;

[0108] 3) when R₃ is tert-butyl and R₅ is hydroxyl, then R₆ is not4-tert-butyl;

[0109] b) when R₁ is

[0110]  then none of R₂, R₃ and R₄ is C₁-C₄ alkyl, the other two of R₂,R₃ and R₄ being hydrogen; and

[0111] an antimicrobial effective carrier.

[0112] The present invention also provides a method of reducing thepresence of microorganisms on a substrate comprising treating thesubstrate with an effective amount of at least one antimicrobialcompound of Formula (II).

[0113] The above antimicrobial compounds of Formula (II), are preferablyincorporated in an antimicrobial composition of the present invention inan amount of about 0.0001 to 10, more preferably from about 0.001 to 5%by weight.

[0114] The antimicrobial compositions of the present invention may beincorporated into products having a variety of vehicles for applicationto the skin or tissue surfaces including creams, lotions, foundations,cleansing lotions, soaps, shampoos, ointments, syrups and suspensions.Compositions may comprise, for example, aqueous or oily solutions ordispersions, oil-in-water or water-in-oil emulsions, pastes, gels orsolids. Topically or orally acceptable carriers and excipients of use insuch preparations will be well known to those skilled in the art.

[0115] The antimicrobial compositions of the present invention may beincluded in products which are developed for the treatment ofmicroorganism-instigated conditions such as deodorant and/orantiperspirant preparations, antibacterial skin washes, anti-acnepreparations, impregnated materials (e.g. wound dressings, sutures, anddental floss), pharmaceuticals, opthalmic preparations and sterilants.

[0116] Typically, a deodorizing composition reduces or prevent body odorby reducing perspiration (e.g. often referred to as an antiperspirantcomposition) or the presence of microorganisms on the surface of theskin.

[0117] Antiperspirant compositions often comprise a metal salt, such asaluminum or zirconium salts which blocks the pores of the skin.Typically, such compositions, however, reduce perspiration by no morethan 50%. It is well known that sweat is odorless until it has beendegraded by the skin microflora. Typical deodorant compositions includeethanol and/or Triclosan (2′,4,4′-trichloro,2-hydroxy-diphenyl ether)which are a well known antimicrobial compounds. However, the deodorizingeffect obtained with such deodorant compositions is transitory and theconcentration of microorganisms may reach previous levels shortly afterapplication.

[0118] The invention provides a deodorant composition for topicalapplication to human skin comprising at least one antimicrobial compoundof Formula (II) in an acceptable carrier in which the composition atleast reduces the presence of microorganisms and/or their malodorousmetabolic processes for greater than a transitory period of time.

[0119] Such deodorant compositions in addition to containing thecomposition of the present invention contain a low molecular weightaliphatic alcohol, preferably containing up to 4 carbons and especiallya monohydric alcohol such as ethanol, which can act in combination withthe antimicrobial compounds of Formula (II) to provide an effectivedeodorant composition. The amount of the alcohol in the composition istypically selected within the range of from about 10 to 80% by weight,preferably from about 30 to 70% by weight.

[0120] The deodorant composition according to the present invention mayalso comprise other materials commonly found in deodorant orantiperspirant compositions. In practice, the present compositionusually contains at least one acceptable carrier in addition to theantimicrobial compound of Formula (II) alone or in combination with analcohol. The carrier may comprise a liquid vehicle such as an alcohol asdescribed hereinbefore, in addition to water, a hydrophobic vehiclewhich may for example be a volatile or non-volatile silicone oil, aliquid hydrocarbon, a water-insoluble alcohol, an aliphatic ether, analiphatic or aromatic ester. The carrier is typically present in anamount of from about 10 to 80% by weight based on the total weight ofthe composition.

[0121] Other additives may include fragrances in an amount of from about0 to 2% by weight, antiperspirant actives such as aluminum or zirconiumcompounds in an amount of from about 0 to 40% by weight, preferably fromabout 5 to 28% by weight, skin softening agents such as silicone oils orsolid silicone polymers, in an amount of from about 0 to 20% by weight,coloring agents in an amount of from about 0 to 2% by weight,humectants, such as sorbitol or glycerol, in an amount of from about 0to 10% by weight, thickening agents such as starches or cellulosederivatives, in an amount from about 0 to 5% by weight, gellants such asdibenzoyl sorbitol, hydroxystearic acid, stearyl alcohol, or amidederivatives of tricarboxylic acids, in an amount of from about 0 to 15%by weight, suspension agents, such as clays or silicas, in an amount ofup to about 5% by weight, structurants such as silicone elastomers orsilicone or hydrocarbon waxes, in an amount of about 0 to 15% by weight,propellants, such as hydrocarbons having a boiling point of below 10°C., e.g. butane and propane isomers, in an amount of from about 30 to95% by weight, and other cosmetic additives conventionally employed insuch compositions. Where water and a hydrophobic material is present,the composition preferably contains an emulsifier/system such aspolyethoxylate ethers or esters. The use of such substances and theproportions in which they are incorporated depend on the form of thecomposition which may be an aerosol, stick, roll-on, gel, lotion, cream,ointment, powder, suspension or soap.

[0122] Gels are transparent, semi-solid, colloidal systems where thewater is restricted by an interlacing network of solvated particles. Thegels useful in the present invention may have a wide range ofviscosities, e.g., from about 4,000 to about 200,000 centipoise,however, since they are formulated for topical use, the compositionswill generally have relatively high viscosities (i.e., they will beself-supporting).

[0123] The formulation of aqueous gels requires the presence of waterand generally requires the use of a compatiblepharmaceutically-acceptable gelling agent in the compositions of thepresent invention. Preferred compositions contain at least about 15%water, and may additionally contain an alcohol or mixture of alcohols(e.g., C₁-C₁₄) in a water:alcohol ratio of from about 5:1 to about100:1. The gelling agent will generally be present at about 0.25% toabout 10% of the composition. Desirable gels may be formed using anacidic carboxy polymer as the gelling agent, together with a compatibleneutralizing agent. Pharmaceutically-acceptable acidic carboxy polymersinclude, for example, Carbopol compounds (a range of carboxypolymethylenes commercially available from B. F. Goodrich Chemicals,Cleveland, Ohio) and the neutralizing compounds include, for example,diisopropyl amine, sodium hydroxide, and beta-alanine. Surface activeagents or surfactants, especially nonionic surfactants, such as ethyleneoxide/propylene oxide block copolymers (commercially available asPluronics from BASF Wyandotte Corp.), and/or ethylene glycol orpropylene glycol may also be included in the compositions to help in theformation of the gel and to act as dispersing agents for the activecomponents.

[0124] Aqueous lotions of the present invention are formulated in thesame way as the above-described gels, except that they have lowerviscosities (i.e., below about 4,000 centipoise) and do not include thegelling agent. Lotions are liquid preparations intended for externalapplication to the skin. Most lotions contain finely powdered substancesthat are insoluble in the dispersion medium and are suspended throughthe use of suspending or dispersing agents. Other lotions have, as thedispersed liquid phase, liquid substances that are immiscible with thevehicle and are usually dispersed by means of emulsifying agents orother suitable stabilizers. Depending upon the nature of theingredients, lotions may be prepared in the same manner as suspensions,emulsions or solutions. The fluidity of lotions permits their rapid anduniform application over a wide surface area.

[0125] The compositions of the present invention may additionallycontain, at their art-established usage levels, compatible adjunctcomponents conventionally used in the formulation of topicalcompositions. These adjunct components include, but are not limited to,active materials (such as supplementary antimicrobial oranti-inflammatory ingredients) or ingredients used to enhance theformulation, itself (such as excipients, dyes, perfumes, thickeningagents, skin penetration enhancers, stabilizers, preservatives, andantioxidants). The compositions of the present invention may alsocontain, in an amount which can range from about 1% to about 99.5% ofthe compositions, compatible pharmaceutical carrier materials especiallyadapted for topical application and formulation into an aqueous lotionor gel. Carrier materials suitable for use in the instant compositionsinclude those well-known for use in the cosmetic and medical arts.Suitable carriers include, for example, water, liquid alcohols, liquidglycols, liquid polyalkalene glycols, liquid esters, liquid amines,liquid protein hydrolysates, liquid alkalated protein hydrolysates,liquid lanolin and lanolin derivatives, and like materials.

[0126] More preferred compositions include those represented for use inan oral cavity comprising an antimicrobial effective amount of at leastone antimicrobial compound of Formula (III):

[0127] wherein

[0128] R₁ is selected from the group

[0129] R₂ and R₃ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkylgroup; an alkyl group substituted with phenyl in which phenyl isoptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group; phenyl optionally substituted with a memberselected from the group consisting of an alkyl group, a cycloalkylgroup, a hydroxyalkyl group, and a hydroxycycloalkyl group; and benzyloptionally substituted with a member selected from the group consistingof an alkyl group, a cycloalkyl group, a hydroxyalkyl group, and ahydroxycycloalkyl group;

[0130] R₄ is selected from the group consisting of hydrogen, an alkylgroup, a cycloalkyl group, benzyl, and phenyl;

[0131] R₅ is selected from the group consisting of hydroxyl, benzyl,alkoxy, hydroxyalkyl, and cycloalkyl optionally substituted withhydroxyl; and

[0132] R₆ and R₇ are each independently selected from the groupconsisting of hydrogen; an alkyl group; a cycloalkyl group; an alkenylgroup; a cycloalkenyl group; benzyl, an alkoxy group; phenyl optionallysubstituted with an alkyl group, a cycloalkyl group, an alkenyl group, acycloalkenyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;an alkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenoxy; and benzyloxy;

[0133] with the proviso that

[0134] a) when R₁ is

[0135]  then each of R₂, R₃, R₄, and R₆ is not hydrogen; and

[0136] b) when R₁ is

[0137]  then none of R₂, R₃ and R₄ is C₁-C₄ alkyl, the other two of R₂,R₃ and R₄ being hydrogen; and

[0138] an orally acceptable carrier.

[0139] The present invention further provides a method of reducingmicroorganisms in an oral cavity which comprises administering to theoral cavity an oral composition having an effective amount of at leastone antimicrobial compound of Formula (III).

[0140] The antimicrobial compounds of Formula (III) may be present in anoral composition of the present invention preferably in an amount offrom about 0.0001 to 10%, more preferably from about 0.001 to 5% byweight.

[0141] The use of the antimicrobial compounds according to the inventionin oral compositions is particularly advantageous because they provideeffective results against a broad range of microorganisms known to bepresent in the oral cavity.

[0142] A preferred group of antimicrobial compounds from Formulas I-IIIuseful in the antimicrobial and/or oral compositions of the presentinvention includes 2-(2-Hydroxy-4-methylPhenoxy)-5-ethylPhenol,2-(2-HydroxyPhenoxy)-5-heptylPhenol, 2-(2-HydroxyPhenoxy)-5-octylPhenol,2-but-2-enyl-6-(2-methoxyphenoxy)phenol,2-(2-methoxyphenoxy)-6-butylphenol,2-(2-hydroxyphenoxy)-6-(3-hydroxypropyl)phenol,6-(2-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxy-1-methylpropyl)-2-(2-hydroxyphenoxy)phenol,6-(3-hydroxy-1-methylpropyl)-2-(2-methoxyphenoxy)phenol,2-(2-hydroxyphenoxy)-6-(2-hydroxycyclohexyl)phenol,2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol,2-(2-methoxyphenoxy)-6-prop-2-enylphenol,2-(2-methoxyphenoxy)-6-(1-methylprop-2-enyl)phenol,2-(2-methoxyphenoxy)-6-propylphenol, 2-tert-butyl-6-phenylmethoxyphenol,2-(4-(1-methyl-1-ethylpropyl)-phenylmethoxy)phenol,2-phenylmethoxy-4-cyclohexylphenol,2-(2-hydroxy-4-tert-butylphenoxy)-6-propylphenol,2-(2-hydroxyphenoxy)-5-cyclohexylmethylphenol,2-(2-hydroxyphenoxy)-6-cyclohexylphenol,2-(2-methoxyphenoxy)-6-but-2-enylphenol,2-(2-methoxyphenoxy)-5-phenylmethylphenol.

[0143] Oral compositions which contain antimicrobial compounds of thepresent invention may be in the form of mouthwashes, gargles,dentifrices, dispersible oral films, oral film-forming dentifrices,anti-plaque compositions and as general antiseptic compositions, forexample, in the form of denture cleansing tablets or solutions. The oralcompositions of the present invention may, if desired, further compriseone or more additional active ingredients and formulations containingsuch, as conventionally used in the art. These include, for example,anti-plaque agents such as bromochlorophene, triclosan, cetylpyridiniumchloride, chlorhexidine salts, and essential oils such as thymol,menthol, and the like, fluoride ion sources such as sodium fluoride,sodium monofluorophosphate and amine fluorides, anti-tartar compoundssuch as zinc salts, preferably zinc citrate, and water solublepyrophosphate salts, preferably alkali metal pyrophosphates, anddesensitizing agents which reduce tooth sensitivity including potassiumsalts such as potassium nitrate and potassium chloride and strontiumsalts such as strontium chloride and strontium acetate.

[0144] One particular formulation comprising essential oils is soldcommercially as LISTERINE® which composition is exemplified in Pan etal. (U.S. Pat. No. 6,121,315), and which reference includes effectiveessential oil formulations having anti-plaque activity. The contents ofU.S. Pat. No. 6,121,315 is hereby incorporated by reference in itsentirety. The essential oil formulation, optionally contained in theoral compositions of the present invention, preferably comprises fromabout 0.005% to 0.5% by weight of thymol, from about 0.005% to 0.5% byweight of menthol, from about 0.005% to 0.5% by weight of eucalyptol,and from about 0.005% to 0.5% by weight of methyl salicylate.

[0145] The compositions according to the invention may alternatively beprovided in concentrated form, for example as a powder, anhydroussolution or effervescent tablet formulation, suitable for dilution inwater prior to use as a sterilant of, for example, dental instruments.One preferred use of the anti-microbial compositions of the invention isas toothbrush sanitizers, designed to reduce microbiologicalcontamination of toothbrush heads, for example by overnight soaking asneeded, typically every 1 to 14 days of use. A substantial reduction inmicroorganism contamination may be achieved in this way withoutsignificant adverse effects on the toothbrush or other dentalinstrument.

[0146] Antimicrobial enhancing agents may be included in the oralcompositions of the present invention. Incorporating such antimicrobialenhancing agent into compositions containing antimicrobial compounds areknown in the art, as described for example in U.S. Pat. Nos. 5,188,821and 5,192,531. The term antimicrobial enhancing agent” as used hereinrefers to organic compounds which contains a delivery-enhancing groupand a retention-enhancing group which together acts to improve thesanitizing effectiveness of the antimicrobial agent. As used herein, thedelivery-enhancing group refers to one which attaches or substantively,adhesively, cohesively or otherwise bonds the antimicrobial enhancingagent (carrying the antimicrobial agent) to oral surfaces such as toothand gum, thereby □delivering□ the antimicrobial agent to such surfaces.The retention-enhancing group, generally hydrophobic, attaches orotherwise bonds the antimicrobial agent to the antimicrobial enhancingagent, thereby promoting retention of the antimicrobial agent to theantimicrobial enhancing agent and indirectly on the oral surfaces. Theactive retention of the antimicrobial agent on the oral surfacesenhances the disinfecting effect on oral surfaces.

[0147] In the preferred form, the antimicrobial enhancing agent includesan anionic polymer comprising a chain or backbone containing repeatingunits each preferably containing at least one carbon atom and preferablyat least one directly or indirectly pendent, monovalentdelivery-enhancing group, and at least one directly or indirectlypendent, monovalent retention-enhancing group geminally, vincinally, orless preferably otherwise bonded to atoms, preferably carbon, in thechain.

[0148] The antimicrobial enhancing agent may be a simple compound suchas a polymerizable monomer, or more preferably a polymer includingoligomers, homopolymers, copolymers of two or more monomers, ionomers,block copolymers, graft copolymers, cross-linked polymers andcopolymers, and the like. The antimicrobial enhancing agent may benatural or synthetic, and water-insoluble or preferably water soluble orswellable, having an average molecular weight of from about 100 to5,000,000, preferably from about 1,000 to 1,000,000, more preferablyfrom about 25,000 to 500,000.

[0149] Preferable antimicrobial enhancing agents for use in the practiceof the present invention include a natural or synthetic anionicpolymeric polycarboxylate having a molecular weight of from about 1,000to 5,000,000, preferably from about 30,000 to 500,000. Synthetic anionicpolymeric polycarboxylates are generally employed in the form of theirfree acids or preferably partially or more preferably fully neutralizedwater soluble alkali metal such as potassium and sodium, or ammoniumsalts. Preferred are 1:4 to 4:1 copolymers of maleic anhydride or acidwith another polymerizable ethylenically unsaturated monomer, preferablymethyl vinyl ether/maleic anhydride having a molecular weight of fromabout 30,000 to 1,000,000, most preferably from about 30,000 to 500,000.These copolymers are available, for example, as GANTREZ®, AN 139(molecular weight 500,000), AN 119 (molecular weight 250,000), andpreferably S-97 Pharmaceutical Grade (molecular weight 700,000), fromISP Technologies, Inc., Bound Brook, N.J. 08805.

[0150] Other useful polymeric polycarboxylates containing or modified tocontain retention-enhancing groups include the 1:1 copolymers of maleicanhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available, forexample, as Monsanto EMA® No. 1103 (molecular weight 10,000), and Grade61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethylmethacrylate, methyl or ethyl acrylate, isobutyl methacrylate, isobutylvinyl ether or □vinyl-2-pyrrolidone. Additional polycarboxylatecompounds containing or modified to contain retention-enhancing groupsinclude copolymers of maleic anhydride with styrene, isobutylene orethyl vinyl ether, polyacrylic, polyitaconic and polymaleic acids, andsulfonacrylic oligomers with a molecular weight as low as 1,000available as UNIROYAL® ND-2.

[0151] Also useful in the practice of the present invention are theso-called carboxyvinyl polymers, commercially available, for example,under the trademarks CARBOPOL□ 934, 940, and 941 from B.F. Goodrich,Cleveland, Ohio 44131, these polymers consisting of a colloidallywater-soluble polymer of polyacrylic acid crosslinked with from about0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol asa crosslinking agent, often with molecular weights of up to 4-5 millionor more.

[0152] Polysiloxanes containing or modified to contain pendentdelivery-enhancing groups and retention-enhancing groups such as liquidsilicone oils such as diphenyl or di(C₁-C₄)alkyl polysiloxanes andparticularly dimethyl-polysiloxane, may also be employed in the practiceof the present invention.

[0153] Also effective herein are ionomers containing or modified tocontain delivery- and retention-enhancing groups. Ionomers are describedon pages 546-573 of the Kirk Othmer Encyclopedia of Chemical Technology,Third Edition, Supplement Volume, John Wiley & Sons, copyright 1984,which description is incorporated herein by reference. Also effectiveherein, provided that contain or are modified to containingretention-enhancing groups, are polyesters, polyurethanes, and syntheticand natural polyamides including proteins and proteinaceous materialssuch as collagen, poly(arginine) and other polymerized amino acids.

[0154] The antimicrobial enhancing agent, when employed, is incorporatedin the compositions of the present invention in weight amounts of fromabout 0.05 to about 5%, preferably from about 0.1 to 3%.

[0155] Fluoride ions may also be included in the oral compositions ofthe present invention. Fluoride ions are implicated in the prevention ofdental caries and may also serve as a tooth-hardening agent. An amountof fluoride ions suitable for use in an oral composition of the presentinvention is from 25 ppm to 5,000 ppm.

[0156] Fluoride ion producing compounds vary in degree of watersolubility. They release fluoride ions in water and do not generallyreact with other compounds of the oral composition. Among the fluorideion producing compounds are inorganic fluoride salts, such as solublealkali metal, alkaline earth metal salts, for example, sodium fluoride,potassium fluoride, ammonium fluoride, calcium fluoride, cuprousfluoride, zinc fluoride, barium fluoride, sodium monofluorophosphate,aluminum mono- and di-fluorophosphate and sodium calciumfluorophosphate. Alkali metal and tin fluorides, such as sodium andstannous fluorides, sodium monofluorophosphate (MFP) and mixturesthereof, are preferred.

[0157] The amount of fluoride ion producing compound is dependent uponthe type of compound, its solubility in water, and the type of oralcomposition. A non-toxic amount of such compound is generally in therange from about 0.0005 to 3.0% by weight based on the total weight ofthe oral composition. Any suitable minimum amount of such compounds maybe used, but it is preferable to employ a sufficient amount of thefluoride ion producing compounds to provide from about 300 to 2,000 ppm,more preferably from about 800 to about 1,500 ppm of fluoride ion to theoral cavity.

[0158] Typically, for sodium fluoride, the desired amount up to about 2%by weight, based on the total weight of the composition, and preferablyin an amount of from about 0.05 to 1%, more preferably from about 0.2 to0.35% by weight. Typically for sodium monofluorophosphate, the compoundis desirably present in an amount of from about 0.1 to 3%, morepreferably about 0.76% by weight.

[0159] The oral composition of the present invention may be in the formof a solution such as a mouthrinse and may be in the form of asemi-solid such as a toothpaste, a gel dentifrice (which may containfrom about 0 to 75% by weight of a polishing agent), a chewing gum, adispersible oral film, a film-forming dentifrice, a solid lozenge or thelike. Oral gel preparations typically contain a siliceous polishingmaterial including crystalline silica having particle sizes of up to 5microns, silica gel, colloidal silica or complex amorphous alkali metalaluminosilicate or combinations thereof.

[0160] When visually clear or opacified gels are employed, a polishingagent of colloidal silica or alkali metal aluminosilicate complexes(that is, silica containing alumina combined in its matrix) areparticularly useful, since they are consistent with gel-like texture andhave refractive indices close to the refractive indices of gellingagent-liquid (including water and/or humectant) systems commonly used indentifrices.

[0161] Where the oral composition of the present invention is a gel orpaste, an orally acceptable carrier, including a water-phase withhumectant which is preferably glycerine or sorbitol or an alkyleneglycol such as polyethylene glycol or propylene glycol is present. Wherewater is typically present in an amount of from about 15 to 40% byweight and glycerine, sorbitol and/or the alkylene glycol (preferablypropylene glycol) are preferably in an amount of from about 20 to 75% byweight, preferably about 25 to 60% by weight based on the total weightof the composition.

[0162] When the oral composition is substantially semi-solid or pasty incharacter, such as a toothpaste (dentifrice), the orally acceptablecarrier of the dentifrice may contain a dentally acceptable polishingmaterial such as sodium bicarbonate, sodium metaphosphate, potassiummetaphosphate, tricalcium phosphate, dihydrated dicalcium phosphate,anhydrous dicalcium phosphate, calcium pyrophosphate, calcium carbonate,aluminum silicate, hydrated alumina, silica, bentonite, and mixturesthereof alone or with minor amounts of hard polishing material such ascalcined alumina and/or zirconium silicate. Preferred polishingmaterials include sodium bicarbonate, silica, sodium metaphosphate,dicalcium phosphate, calcium pyrophosphate and hydrated alumina.

[0163] The polishing material is generally present in the oralcomposition in an amount of from about 10% to 75% by weight, preferablyfrom about 10% to 30% by weight in a gel, and preferably from about 25%to 75% by weight in a cream or paste.

[0164] Toothpastes or dental cream dentifrices as well as geldentifrices typically contain a natural or synthetic thickener orgelling agent in an amount of from about 0.1 to 10% by weight,preferably from about 0.5 to 5% by weight.

[0165] Suitable thickeners or gelling agents include Irish moss,iota-carrageenan, kappa-carrageenan, gum tragacanth, starch,polyvinylpyrrolidone, xanthan gum, hydroxyethyl propyl cellulose,hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose,hydroxyethyl cellulose and sodium carboxymethyl cellulose.

[0166] Where the oral composition is a liquid such as a mouthwash orrinse, the liquid carrier is typically a water-alcohol mixture.Generally, the weight ratio of water to alcohol is in the range of fromabout 3:1 to 20:1 and preferably from about 4:1 to 10:1. The alcohol isa non-toxic alcohol such as ethanol or isopropanol. A humectant such asglycerine, sorbitol or an alkylene glycol such as polyethylene glycol orpreferably propylene glycol may be present in an amount of from about 10to 30% by weight. Mouthrinses typically contain about 50 to 85% ofwater, from about 0 to 20% by weight of a non-toxic alcohol and fromabout 10 to 40% by weight of a humectant.

[0167] Organic surface-active agents may be used in the compositions ofthe present invention to achieve increased antimicrobial action, andassist in achieving thorough and complete dispersion of theantimicrobial compound of Formula (III) throughout the oral cavity. Theorganic surface-active material is preferably anionic, nonionic orampholytic in nature, and imparts to the composition detersive andfoaming properties. Suitable examples of anionic surfactants arewater-soluble salts of higher fatty acid monoglyceride monosulfates,such as the sodium salt of the monosulfated monoglyceride ofhydrogenated coconut oil fatty acids, higher alkyl sulfates such assodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate, higher alkyl sulfoacetates, higher fatty acid estersof 1,2-dihydroxy propane sulfonate, and the substantially saturatedhigher aliphatic acyl amides of lower aliphatic amino carboxylic acidcompounds, such as those having 12 to 16 carbons in the fatty acid,alkyl or acyl radicals and alkoyl taurines, and the like. Examples ofsuch compounds include N-lauroyl sarcosine, and the sodium, potassiumand ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoylsarcosine which are substantially free from soap or similar higher fattyacid material as well as N-methyl-N-cocoyl (or oleoyl or palmitoyl)taurines. The use of sarcosinate compounds in the oral compositions ofthe present invention is typically advantageous since these materialsexhibit a prolonged and marked effect in the inhibition of acidformation in the oral cavity due to carbohydrate breakdown in additionto exerting some reduction in the solubility of tooth enamel in acidsolutions.

[0168] Examples of water-soluble nonionic surfactants are condensationproducts of ethylene oxide with various reactive hydrogen-containingcompounds reactive therewith having long hydrophobic chains (e.g.aliphatic chains of about 12 to 20 carbon atoms), which condensationproducts (“ethoxamers”) contain hydrophilic polyoxyethylene moieties,such as condensation products of poly(ethylene oxide) with fatty acids,fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitanmonostearate) and polypropyleneoxide.

[0169] Amphoteric surface active agents have the capacity to behave aseither an acid or a base, depending upon pH, and comprise a diversegroup of compounds, such as polypeptides, proteins, phospholipids, andbetaines. Alkyl betaines, e.g., alkyl dimethyl betaines which includedecyl betaine and 2-(N-decyl-N,N-dimethylammonio) acetate, myristylbetaine, palmityl betaine, lauryl betaine, cetyl betaine, stearylbetaine, and the like, are particularly preferred. Betaine surfaceactive agents may be present in the oral composition of the presentinvention in an amount typically from about 0.01% to about 2.0% byweight.

[0170] Examples of polyoxamers useful in the practice of the presentinvention include block copolymers of polyoxyethylene andpolyoxypropylene having an average molecular weight of from about 3000to 5000 and a preferred average molecular weight of from about 3500 to4000, and containing from about 10 to 80% by weight of hydrophilicpolyoxyethylene groups of the block copolymer.

[0171] Natural and artificial sweeteners may be used in the oralcompositions. The sweetener may be selected from a wide range of wellknown materials including naturally occurring water-soluble sweeteners,artificial water-soluble sweeteners and modified water-solublesweeteners derived from naturally occurring water-soluble sweeteners.Artificial water-soluble sweeteners include, but are not limited to,soluble saccharin salts, e.g., sodium or calcium saccharin salts,cyclamate salts, the sodium, ammonium or calcium salt of3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide, the potassiumsalt of 3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide(Acesulfame-K), the free acid form of saccharin and dipeptide basedsweeteners, such as L-aspartic acid derived sweeteners. Dipeptidesweeteners include L-aspartyl-L-phenylalanine methyl ester (Aspartame)and materials described in U.S. Pat. No. 3,492,131,L-alpha-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamidehydrate (Alitame), methyl esters of L-aspartyl-L-phenylglycerine andL-aspartyl-L-2,5-dihydrophenylglycine,L-aspartyl-2,5-dihydro-L-phenylalanine andL-aspartyl-L-(1-cyclohexene)-alanine. Naturally occurring water-solublesweeteners include, but are not limited to, sugar alcohols, includingsorbitol as 70% sorbitol solution, mannitol, xylitol, maltitol,hydrogenated starch hydrolysates and mixtures thereof.

[0172] Water-soluble sweeteners derived from naturally occurringwater-soluble sweeteners include, but are not limited to, chlorinatedderivatives of sucrose, known, for example, under the productdesignation of Sucralose, and protein-based sweeteners such asthaumaoccous danielli (Thaumatin I and II).

[0173] Sorbitol solution supplies sweetness and body to the compositionand gives a desirable mouth feel. Sorbitol solution also enhancesflavor, prevents harsh taste and provides a fresh and lively sensationin the mouth. It also adds body and serves as a humectant.

[0174] In general, an effective amount of sweetener is utilized toprovide the level of sweetness desired in any particular embodiment ofthe oral compositions according to the present invention. This amountwill vary with the sweetener selected and the final form of the oralcomposition. The amount of sweetener normally present is from about0.0025% by weight to about 60% by weight of the oral composition. Theexact range of amounts for each type of sweetener in an oral compositionis readily determined by those skilled in the art.

[0175] The flavors that may be used in the invention include natural andartificial flavors known in the art. Suitable flavors include, but arenot limited to, mints, such as peppermint, citrus flavors such as orangeand lemon, artificial vanilla, cinnamon, various fruit flavors, and thelike. Anethole (or anise camphor, p-propenyl anisole) is a flavorconstituent of anise and fennel oils that are used widely as flavoringagent and antiseptic and was found useful in masking the harsh taste ofthymol.

[0176] The amount of flavor is normally a matter of preference subjectto the type of final oral composition, the individual flavor employedand the strength of flavor desired. The flavors are preferably utilizedin amounts that may range of from about 0.01% to about 6% by weight ofthe oral composition.

[0177] Coloring agents are used in amounts effective to produce an oralcomposition of the desired color. These coloring agents may beincorporated in amounts up to about 3% by weight of the oralcomposition. The coloring agents may also include natural food colorsand dyes suitable for food, drug and cosmetic applications. Thesecoloring agents are known as FD & C dyes and lakes. The coloringmaterials are preferably water-soluble. Illustrative nonlimitingexamples include the indigoid dye known as FD & C Blue No. 1, and D & CYellow No. 10. A full recitation of all FD & C colorants and theircorresponding chemical structures may be found in the Kirk-OthmerEncyclopedia of Chemical Technology, 3rd Edition, in volume 5 at pages857-884. A preferred opacifier, titanium dioxide, may be incorporated inamounts up to about 2.0% by weight, preferably less than about 1.0% byweight based on the total weight of the composition and most preferablyless than about 0.4% by weight.

[0178] Desensitizing agents used to diminish teeth sensitivity such asstrontium is chloride, potassium nitrate and potassium citrate may alsobe included in the oral compositions of the present invention atconcentrations of from about 0.1 to 10% by weight.

[0179] Various other materials may be incorporated in the oralcompositions of the invention including whitening agents such as ureaperoxide and hydrogen peroxide, preservatives, such as sodium benzoate,chlorophyll compounds and/or ammoniated compounds such as urea,diammonium phosphate, and mixtures thereof. These adjuvants, whenpresent, are incorporated in the compositions in amounts which do notsubstantially adversely affect the desired properties.

[0180] The oral compositions of the present invention may be prepared bysuitably mixing the ingredients. By way of example, in the preparationof a mouthrinse, the antimicrobial compound of Formula (III) may bedispersed in a mixture containing for example, alcohol, humectant,surfactant, and salts such as sodium fluoride and potassium phosphate,and a flavoring is then added and the resulting combination mixedthoroughly. Dentifrices are prepared in a similar manner with theaddition, typically, of a thickener and a polishing agent.

[0181] The oral compositions of the present invention may beincorporated into dispersible oral films, oral film forming dentifrices,lozenges, or in chewing gum or other products, e.g. by stirring into awarm gum base or coating the outer surface of a gum base, illustrativeof which may be mentioned jelutone, rubber latex, vinylite resins, andthe like, desirably with conventional plasticizers or softeners, sugaror other sweeteners or carbohydrates such as glucose, sorbitol and thelike.

[0182] Oral film forming dentifrices include materials that may beapplied to dental and/or oral surfaces in a manner to form a film orcoating for reducing physical access to such surfaces by microorganisms,acid, food residues, debris, and the like, and for preventing growth ofharmful microorganisms. The resulting oral film thus provides aprotective physical barrier and enhances delivery of antimicrobialagents for minimizing attachment, propagation, growth or colonization ofbacteria on the dental surfaces. Such compositions may be water-soluble.Suitable oral film forming substances include silicone compounds,aminoalkyl silicones, organopolysiloxanes, dimethyl polysiloxanes,alkyl-dimethicone copolyols, alkoxy-dimethicone copolyols, cyclicsiloxane polymers and like substances.

[0183] The vehicle or carrier for a tablet or lozenge is desirably anon-cariogenic solid water-soluble polyhydric alcohol (polyol) such asmannitol, xylitol, sorbitol, malitol, a hydrogenated starch hydrolysate,Lycasin, hydrogenated glucose, hydrogenated disaccharides orhydrogenated polysaccharides, in an amount of from about 90 to 98% byweight. Solid salts such as sodium bicarbonate, sodium chloride,potassium bicarbonate or potassium chloride may totally or partiallyreplace the polyol carrier.

[0184] Tableting lubricants, in minor amounts of from about 0.1 to 5% byweight, may be incorporated into the tablet or lozenge formulation tofacilitate the preparation of both the tablets and lozenges. Suitablelubricants include vegetable oils such as coconut oil, magnesiumstearate, aluminum stearate, talc, starch and Carbowax.

[0185] Lozenge formulations contain about 2% gum as a barrier agent toprovide a shiny surface as opposed to a tablet which has a smoothfinish. Suitable non-cariogenic gums include kappa carrageenan,carboxymethyl cellulose, hydroxyethyl cellulose, and the like.

[0186] The lozenge or tablet may optionally be coated with a coatingmaterial such as waxes, shellac, carboxymethyl cellulose,polyethylene/maleic anhydride copolymer or kappa-carrageenan to furtherincrease the time it takes the tablet or lozenge to dissolve in themouth. The uncoated tablet or lozenge is slow dissolving, providing asustained release rate of active ingredients of about 3 to 5 minutes.Accordingly, the solid dose tablet and lozenge composition of thisinvention affords a relatively longer time period of contact of theteeth in the oral cavity with the active ingredients.

[0187] Dispersible oral film formulations contain an antimicrobialcompound of Formula (III) in a carrier comprising one or morewater-soluble polymers in combination with certain ingredients andprovides a therapeutic and/or cosmetic effect. The film is coated anddried utilizing existing coating technology and exhibits instantwettability followed by rapid dissolution/disintegration uponadministration in the oral cavity.

[0188] The foregoing discussion discloses and describes merely exemplaryembodiments of the present invention. One skilled in the art willreadily recognize from such discussion that various changes,modifications and variations can be made therein without departing fromthe spirit and scope of the invention as defined in the followingclaims.

EXAMPLE 1 Mouthrinse Composition Containing Antimicrobial Compounds ofFormula (III)

[0189] A mouthrinse composition containing the ingredients and theamounts shown in Table 1 is prepared by mixing the alcohol solubleingredients 2 and 3 with ethanol (alcohol, USP). Water is added to themixture. Water soluble ingredients 4 through 9 are then added andblended thoroughly to the mixture. About 1000 ml of water are added tothe mixture to adjust the final volume to yield the mouthrinsecomposition. The composition of Table 1 may also be prepared using othercompounds falling within the scope of Formula III in place of the6-(3-hydroxy-1-methylpropyl)-2-(2-methoxyphenoxy)phenol. TABLE 1Ingredients % by weight  1) Alcohol, USP 15  2)6-(3-hydroxy-1-methylpropyl)-2-(2- 0.05    methoxyphenoxy)phenol  3)Flavoring oil 0.1  4) Glycerine 3  5) Sodium lauryl methyl cocoyltaurate 0.3  6) Sodium citrate 0.08  7) Citric acid 0.02  8) Saccharinsodium 0.1  9) FD&C Green #3 0.0002 10) Water, USP QS to 100

EXAMPLE 2 Dentifrice Composition Containing Antimicrobial Compounds ofFormula (III)

[0190] A dentifrice composition containing the ingredients and theamounts shown in Table 2 is prepared by combining water, a portion ofthe humectant, the sweetener, the fluoride, and the water solublebuffers together. The remainder of the humectant is separately combinedwith the gum and then added to the initial mixture. Titanium oxide andsilicas are blended and then added to the mixture. The colorant, flavoroil, 6-(3-hydroxy-1-methylpropyl)-2-(2-methoxyphenoxy)phenol and thesurfactant are added and blended with the mixture. The composition ofTable 2 may also be prepared using other compounds falling within thescope of Formula III in place of the6-(3-hydroxy-1-methylpropyl)-2-(2-methoxyphenoxy)phenol. TABLE 2Ingredients % by weight  1) Glycerine 6  2) Sodiumcarboxymethylcellulose 1.2  3) Sorbitol 40  4) Sodiummonofluoriphosphate, USP 0.76  5) Saccharin sodium 1  6) Sodiumphosphate, dibasic 0.03  7) Sodium phosphate, monobasic 0.25  8) Silicondioxide, hydrated 15  9) Titanium dioxide 0.2 10) Flavor oil 2 11)6-(3-hydroxy-1-methylpropyl)-2- 0.5    (2-methoxyphenoxy)phenol 12) FD&CGreen #3 0.0002 13) Water, deionized QS to 100

EXAMPLE 3

[0191] Deodorant Composition Containing Antimicrobial Compounds ofFormula (II)

[0192] A deodorant composition containing the ingredients and theamounts shown in Table 3 is prepared by mixing together the polarsolvent, volatile nonpolar solvent, and the2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol. Gellants are addedto the resulting mixture and agitated. The mixture is heated to atemperature in the range from about 75□ to 100□ C until the gellantsmelted and formed a substantially clear and translucent liquid. Theresulting liquid mixture is slightly cooled prior to adding thefragrance. The resulting liquid mixture is poured into a suitablecontainer and cooled to yield a solid form composition. The compositionof Table 3 may also be prepared using other compounds falling within thescope of Formula II in place of2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol. TABLE 3 Ingredients% by weight 1) Propylene glycol 30 2) Glycerine 2.5 3) Butyl stearate 204) 2-(2-hydroxyphenoxy)-6-(3- 0.5    hydroxycyclohexyl)phenol 5)Propylene glycol monostearate 15 6) Water 32

EXAMPLE 4 Antibacterial Soap Composition Containing AntimicrobialCompounds of Formula (II)

[0193] An antibacterial soap composition containing the ingredients andthe amounts shown in Table 4 is prepared by agitating and mixing theingredients for thorough blending. The composition of Table 4 may alsobe prepared using other compounds falling within the scope of Formula IIin place of 2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol. TABLE 4Ingredients % by weight 1) Sodium lauryl sulfate 67 2) Cocamidopropylbetaine 15 3) Glycerine 1 4) Propylene glycol 1 5)2-(2-hydroxyphenoxy)-6-(3- 1    hydroxycyclohexyl)phenol 6) Fragrance0.2 7) Water QS to 100

EXAMPLE 5 Antibacterial Cream or Ointment Composition ContainingAntimicrobial Compounds of Formula (II)

[0194] An antibacterial cream or ointment composition containing theingredients and amounts shown in Table 5 is prepared by dissolving the2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol into the solvent andsurfactant ingredients. The hydrophobic ingredients are then added tothe resulting mixture and blended. The resulting mixture yields anemulsion having a uniform creamy consistency. The composition of Table 5may also be formed using other compounds falling within the scope ofFormula II in place of2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol. TABLE 5 Ingredients% by weight  1) Glycerine 6  2) Propylene glycol 5.5  3) Sodium laurylsulfate 1  4) Cetyl alcohol 4.5  5) Cetyl palmitate 4  6) Steric alcohol4.5  7) Steric acid 4  8) White petrolatum 5  9)2-(2-hydroxyphenoxy)-6-(3- 1    hydroxycyclohexyl)phenol 10) Water,deionized 64.5

What is claimed is:
 1. The compound of Formula (1):

wherein R₁ is selected from the group

R₂ and R₃ are each independently selected from the group consisting ofhydrogen; an alkyl group; a cycloalkyl group; an alkenyl group; acycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkyl group; analkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenyl optionally substituted with a member selected from thegroup consisting of an alkyl group, a cycloalkyl group, a hydroxyalkylgroup, and a hydroxycycloalkyl group; and benzyl optionally substitutedwith a member selected from the group consisting of an alkyl group, acycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;R₄ is selected from the group consisting of hydrogen, an alkyl group, acycloalkyl group, benzyl, and phenyl; R₅ is selected from the groupconsisting of hydroxyl, benzyl, alkoxy, hydroxyalkyl, and cycloalkyloptionally substituted with hydroxyl; and R₆ and R₇ are eachindependently selected from the group consisting of hydrogen; an alkylgroup; a cycloalkyl group; an alkenyl group; a cycloalkenyl group;benzyl, an alkoxy group; phenyl optionally substituted with an alkylgroup, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, ahydroxyalkyl group, and a hydroxycycloalkyl group; an alkyl groupsubstituted with phenyl in which phenyl is optionally substituted with amember selected from the group consisting of an alkyl group, acycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;phenoxy; and benzyloxy; with the proviso that: a) when R₁ is a

 and R₂ and R₄ are each hydrogen, and 1) when R₃ is hydrogen, then R₆ isnot hydrogen, methyl, tert-butyl, phenyl, or phenoxy; 2) when R₅ ishydroxyl and one of R₃ and R₆ is hydrogen, then the other ot R₃ and R₆is not selected from the group consisting of hydrogen, n-propyl,n-butyl, n-pentyl, 1-methylethyl, 2-methylpropyl, 3-methylbutyl, benzyl,or cyclohexyl; 3) when R₃ and R₆ are each hydrogen, then R₅ is notbenzyl; 4) when R₅ is hydroxyl and R₃ is ethyl, then R₆ is not methyl;5) when R₅ is hydroxyl and R₃ is tert-butyl, then R₆ is not tert-butyl;b) when R₁ is a

 R₃, R₄ and R₆ are each hydrogen, and R₅ is hydroxyl, then R₂ is notselected from the group consisting of phenyl and tert-butyl; c) when R₁is a

 R₅ is hydroxyl, and R₆ is hydrogen, then none of R₂, R₃, and R₄ isC₁-C₄ alkyl, the other two of R₂, R₃, and R₄ being hydrogen; d) when R₁is a

 at least one of R₂, R₃ and R₄ is not hydrogen, and e) when R₁ is a

 each of R₂, and R₃ is hydrogen, R₇ and R₄ is tert-butyl, then R₇ is nothydrogen
 2. The compound of claim 1 wherein each of R₃, and R₆ areselected from the group consisting of straight and branched alkylgroups.
 3. The compound of claim 1 wherein each of R₃, R₅, and R₆ is acycloalkyl group.
 4. The compound of claim 1 further including a memberselected from the group consisting of2-(2-hydroxyphenoxy)-5-heptylphenol, 2-(2-hydroxyphenoxy)-5-octylphenol,2-but-2-enyl-6-(2-methoxyphenoxy)phenol,2-(2-methoxyphenoxy)-6-butylphenol,2-(2-hydroxyphenoxy),6-(3-hydroxypropyl)phenol,6-(2-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxy-1-methylpropyl)-2-(2-hydroxyphenoxy)phenol,6-(1-methyl-3-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,2-(2-hydroxyphenoxy)-6-(2-hydroxycyclohexyl)phenol,2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol,2-(2-methoxyphenoxy)-6-prop-2-enylphenol,2-(2-methoxyphenoxy)-6-(1-methylprop-2-enyl)phenol,2-(2-methoxyphenoxy)-6-propylphenol, 2-tert-butyl-6-phenylmethoxyphenol,2-phenylmethoxy-4-cyclohexylphenol,2-(2-hydroxy-4-tert-butylphenoxy)-6-propylphenol,2-(2-hydroxyphenoxy)-5-cyclohexylmethylphenol,2-(2-hydroxyphenoxy)-6-cyclohexylphenol.
 5. An antimicrobial compositioncomprising an antimicrobial effective amount of at least oneantimicrobial compound of Formula (II):

wherein R₁ is selected from the group

R₂ and R₃ are each independently selected from the group consisting ofhydrogen; an alkyl group; a cycloalkyl group; an alkenyl group; acycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkyl group; analkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenyl optionally substituted with a member selected from thegroup consisting of an alkyl group, a cycloalkyl group, a hydroxyalkylgroup, and a hydroxycycloalkyl group; and benzyl optionally substitutedwith a member selected from the group consisting of an alkyl group, acycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;R₄ is selected from the group consisting of hydrogen, an alkyl group, acycloalkyl group, benzyl, and phenyl; R₅ is selected from the groupconsisting of hydroxyl, benzyl, alkoxy, hydroxyalkyl, and cycloalkyloptionally substituted with hydroxyl; and R₆ and R₇ are eachindependently selected from the group consisting of hydrogen; an alkylgroup; a cycloalkyl group; an alkenyl group; a cycloalkenyl group;benzyl, an alkoxy group; phenyl optionally substituted with an alkylgroup, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, ahydroxyalkyl group, and a hydroxycycloalkyl group; an alkyl groupsubstituted with phenyl in which phenyl is optionally substituted with amember selected from the group consisting of an alkyl group, acycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;phenoxy; and benzyloxy; with the proviso that: a) when R₁ is

 and R₂ and R₄ are each hydrogen, and 1) when R₃ is hydrogen, then R₆ isnot hydrogen or methyl; 2) when R₃ is hydrogen and R₅ is hydroxyl, thenR₆ is not hydrogen; 3) when R₃ is tert-butyl and R₅ is hydroxyl, then R₆is not 4-tert-butyl; b) when R₁ is

 then none of R₂, R₃ and R₄ is C₁-C₄ alkyl, the other two of R₂, R₃ andR₄ being hydrogen; c) when R₁ is a

 then each of R₂, R₃, R₄ and R₇ are not hydrogen; and an antimicrobialeffective carrier.
 6. The antimicrobial composition of claim 5 whereinthe antimicrobial effective carrier is selected from the groupconsisting of water, saline, alcohol, glycerin, propylene glycol,mineral oil, petrolatum, and mixtures thereof.
 7. The antimicrobialcomposition of claim 5 wherein R₁ is

each of R₃ and R₄ are hydrogen, and R₂ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 8. The antimicrobial composition of claim 5wherein R₁ is

each of R₂ and R₄ are hydrogen, and R₃ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 9. The antimicrobial composition of claim 5wherein R₁ is

each of R₂ and R₃ are hydrogen, and R₄ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 10. The antimicrobial composition of claim 5wherein R₁ is

and R₅ is alkoxy.
 11. The antimicrobial composition of claim 10 whereineach of R₃ and R₄ is hydrogen and R₂ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 12. The antimicrobial composition of claim10 wherein each of R₂ and R₄ is hydrogen and R₃ is selected from thegroup consisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 13. The antimicrobial composition of claim10 wherein each of R₂ and R₃ is hydrogen and R₄ is selected from thegroup consisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 14. The antimicrobial composition of claim 5wherein the antimicrobial effective amount is from about 0.0001 to 10%by weight of the total weight of the antimicrobial composition.
 15. Theantimicrobial composition of claim 14 wherein the antimicrobialeffective amount is from about 0.001 to 5% by weight.
 16. Theantimicrobial composition of claim 5 wherein the antimicrobial compoundsof Formula (II) are selected from the group consisting of2-(2-Hydroxy-4-methylPhenoxy)-5-ethylPhenol,2-(2-HydroxyPhenoxy)-5-heptylPhenol, 2-(2-HydroxyPhenoxy)-5-octylPhenol,2-but-2-enyl-6-(2-methoxyphenoxy)phenol,2-(2-methoxyphenoxy)-6-butylphenol,2-(2-hydroxyphenoxy)-6-(3-hydroxypropyl)phenol,6-(2-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxy-1-methylpropyl)-2-(2-hydroxyphenoxy)phenol,6-(3-hydroxy-1-methylpropyl)-2-(2-methoxyphenoxy)phenol,2-(2-hydroxyphenoxy)-6-(2-hydroxycyclohexyl)phenol,2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol,2-(2-methoxyphenoxy)-6-prop-2-enylphenol,2-(2-methoxyphenoxy)-6-(1-methylprop-2-enyl)phenol,2-(2-methoxyphenoxy)-6-propylphenol, 2-tert-butyl-6-phenylmethoxyphenol,2-(4-(1-methyl-1-ethylpropyl)-phenylmethoxy)phenol,2-phenylmethoxy-4-cyclohexylphenol,2-(2-hydroxy-4-tert-butylphenoxy)-6-propylphenol,2-(2-hydroxyphenoxy)-5-cyclohexylmethylphenol,2-(2-hydroxyphenoxy)-6-cyclohexylphenol,2-(2-methoxyphenoxy)-6-but-2-enylphenol,2-(2-methoxyphenoxy)-5-phenylmethylphenol.
 17. An oral compositioncomprising an antimicrobial effective amount of at least oneantimicrobial compound of Formula (III):

wherein R₁ is selected from the group

R₂ and R₃ are each independently selected from the group consisting ofhydrogen; an alkyl group; a cycloalkyl group; an alkenyl group; acycloalkenyl group; a hydroxyalkyl group; a hydroxycycloalkyl group; analkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenyl optionally substituted with a member selected from thegroup consisting of an alkyl group, a cycloalkyl group, a hydroxyalkylgroup, and a hydroxycycloalkyl group; and benzyl optionally substitutedwith a member selected from the group consisting of an alkyl group, acycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;R₄ is selected from the group consisting of hydrogen, an alkyl group, acycloalkyl group, benzyl, and phenyl; R₅ is selected from the groupconsisting of hydroxyl, benzyl, alkoxy, hydroxyalkyl, and cycloalkyloptionally substituted with hydroxyl; and R₆ and R₇ are eachindependently selected from the group consisting of hydrogen; an alkylgroup; a cycloalkyl group; an alkenyl group; a cycloalkenyl group;benzyl, an alkoxy group; phenyl optionally substituted with an alkylgroup, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, ahydroxyalkyl group, and a hydroxycycloalkyl group; an alkyl groupsubstituted with phenyl in which phenyl is optionally substituted with amember selected from the group consisting of an alkyl group, acycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;phenoxy; and benzyloxy; with the proviso that a) when R₁ is

 then each of R₂, R₃, R₄, and R₆ is not hydrogen; and b) when R₁ is

 then none of R₂, R₃ and R₄ is C₁-C₄ alkyl, the other two of R₂, R₃ andR₄ being hydrogen; and an orally acceptable carrier.
 18. The oralcomposition of claim 17 wherein the orally acceptable carrier isselected from the group consisting of water, saline, alcohol, glycerin,propylene glycol and mixtures thereof.
 19. The oral composition of claim17 wherein R₁ is

each of R₃ and R₄ are hydrogen, and R₂ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 20. The oral composition of claim 17 whereinR₁ is

each of R₂ and R₄ are hydrogen, and R₃ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 21. The oral composition of claim 17 whereinR₁ is

each of R₂ and R₃ are hydrogen, and R₄ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 22. The oral composition of claim 17 whereinR₁ is

and R₅ is alkoxy.
 23. The oral composition of claim 22 wherein each ofR₃ and R₄ is hydrogen and R₂ is selected from the group consisting ofalkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl, alkenyl, phenyl andbenzyl.
 24. The oral composition of claim 22 wherein each of R₂ and R₄is hydrogen and R₃ is selected from the group consisting of alkyl,hydroxyalkyl, cycloalkyl, hydroxycycloalkyl, alkenyl, phenyl and benzyl.25. The oral composition of claim 22 wherein each of R₂ and R₃ ishydrogen and R₄ is selected from the group consisting of alkyl,hydroxyalkyl, cycloalkyl, hydroxycycloalkyl, alkenyl, phenyl and benzyl.26. The oral composition of claim 17 wherein the antimicrobial effectiveamount is from about 0.0001 to 10% by weight of the total weight of theoral composition.
 27. The oral composition of claim 26 wherein theantimicrobial effective amount is from about 0.001 to 5% by weight. 28.An oral composition comprising an antimicrobial effective amount of atleast one antimicrobial compound of Formula (IV):

wherein R₁ is selected from the group consisting of

R₂ and R₃ are each independently selected from the

 group consisting of hydrogen; an alkyl group; a cycloalkyl group; analkenyl group; a cycloalkenyl group; a hydroxyalkyl group; ahydroxycycloalkyl group; an alkyl group substituted with phenyl in whichphenyl is optionally substituted with a member selected from the groupconsisting of an alkyl group, a cycloalkyl group, a hydroxyalkyl group,and a hydroxycycloalkyl group; phenyl optionally substituted with amember selected from the group consisting of an alkyl group, acycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;and benzyl optionally substituted with a member selected from the groupconsisting of an alkyl group, a cycloalkyl group, a hydroxyalkyl group,and a hydroxycycloalkyl group; R₄ is selected from the group consistingof hydrogen, an alkyl group, a cycloalkyl group, benzyl, and phenyl; R₅is selected from the group consisting of hydroxyl, benzyl, alkoxy,hydroxyalkyl, and cycloalkyl optionally substituted with hydroxyl; andR₆ and R₇ are each independently selected from the group consisting ofhydrogen; an alkyl group; a cycloalkyl group; an alkenyl group; acycloalkenyl group; benzyl, an alkoxy group; phenyl optionallysubstituted with an alkyl group, a cycloalkyl group, an alkenyl group, acycloalkenyl group, a hydroxyalkyl group, and a hydroxycycloalkyl group;an alkyl group substituted with phenyl in which phenyl is optionallysubstituted with a member selected from the group consisting of an alkylgroup, a cycloalkyl group, a hydroxyalkyl group, and a hydroxycycloalkylgroup; phenoxy; and benzyloxy; with the proviso that when R₁ is

then each of R₂, R₃, R₄, and R₆ is not hydrogen; and an orallyacceptable carrier.
 29. The oral composition of claim 28 furthercomprising at least one essential oil.
 30. The oral composition of claim29 wherein the essential oil is selected from the group consisting ofthymol, menthol, eucalyptol, methyl salicylate, and combinationsthereof.
 31. The oral composition of claim 30, wherein the essential oilcomprises: an amount of from about 0.005 to 0.5% menthol; an amount offrom about 0.005 to 0.5% eucalyptol; an amount of from about 0.005 to0.5% methyl salicytate; and an amount of from about 0.005 to 0.5%thymol.
 32. The oral composition of claim 28 wherein the antimicrobialcompounds of Formula (IV) are selected from the group consisting of2-(2-Hydroxy-4-methylPhenoxy)-5-ethylPhenol,2-(2-HydroxyPhenoxy)-5-heptylPhenol, 2-(2-HydroxyPhenoxy)-5-octylPhenol,2-but-2-enyl-6-(2-methoxyphenoxy)phenol,2-(2-methoxyphenoxy)-6-butylphenol,2-(2-hydroxyphenoxy)-6-(3-hydroxypropyl)phenol,6-(2-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxypropyl)-2-(2-methoxyphenoxy)phenol,6-(3-hydroxy-1-methylpropyl)-2-(2-hydroxyphenoxy)phenol,6-(3-hydroxy-1-methylpropyl)-2-(2-methoxyphenoxy)phenol,2-(2-hydroxyphenoxy)-6-(2-hydroxycyclohexyl)phenol,2-(2-hydroxyphenoxy)-6-(3-hydroxycyclohexyl)phenol,2-(2-methoxyphenoxy)-6-prop-2-enylphenol,2-(2-methoxyphenoxy)-6-(1-methylprop-2-enyl)phenol,2-(2-methoxyphenoxy)-6-propylphenol, 2-tert-butyl-6-phenylmethoxyphenol,2-(4-(1-methyl-1-ethylpropyl)-phenylmethoxy)phenol,2-phenylmethoxy-4-cyclohexylphenol,2-(2-hydroxy-4-tert-butylphenoxy)-6-propylphenol,2-(2-hydroxyphenoxy)-5-cyclohexylmethylphenol,2-(2-hydroxyphenoxy)-6-cyclohexylphenol,2-(2-methoxyphenoxy)-6-but-2-enylphenol,2-(2-methoxyphenoxy)-5-phenylmethylphenol.
 33. A method of reducing thepresence of microorganisms on a substrate comprising treating thesubstrate with an effective amount of the antimicrobial composition ofclaim
 5. 34. The method of claim 33 wherein the antimicrobial effectivecarrier is selected from the group consisting of water, saline, alcohol,glycerin, propylene glycol, mineral oil, petrolatum, and mixturesthereof.
 35. The method of claim 33 wherein the antimicrobial effectiveamount is from about 0.0001 to 10% by weight.
 36. The method of claim 35wherein the antimicrobial effective amount is from about 0.001 to 5% byweight.
 37. The method of claim 33 wherein the antimicrobial compositionis in the form of a member selected from the group consisting of adeodorant, a soap, an ointment, and a cream.
 38. A method of reducingthe presence of microorganisms in an oral cavity comprisingadministering into the oral cavity an effective amount of the oralcomposition of claim
 17. 39. The method of claim 38 wherein the orallyacceptable carrier is selected from the group consisting of water,saline, alcohol, glycerin, propylene glycol, and mixtures thereof. 40.The method of claim 38 wherein R₁ is

each of R₃ and R₄ are hydrogen, and R₂ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 41. The method of claim 40 wherein R₁ is

each of R₂ and R₄ are hydrogen, and R₃ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 42. The method of claim 40 wherein R₁ is

each of R₂ and R₃ are hydrogen, and R₄ is selected from the groupconsisting of alkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl,alkenyl, phenyl and benzyl.
 43. The method of claim 40 wherein R₁ is

and R₅ is alkoxy.
 44. The method of claim 43 wherein each of R₃ and R₄is hydrogen and R₂ is selected from the group consisting of alkyl,hydroxyalkyl, cycloalkyl, hydroxycycloalkyl, alkenyl, phenyl and benzyl.45. The method of claim 43 wherein each of R₂ and R₄ is hydrogen and R₃is selected from the group consisting of alkyl, hydroxyalkyl,cycloalkyl, hydroxycycloalkyl, alkenyl, phenyl and benzyl.
 46. Themethod of claim 43 wherein each of R₂ and R₃ is hydrogen and R₄ isselected from the group consisting of alkyl, hydroxyalkyl, cycloalkyl,hydroxycycloalkyl, alkenyl, phenyl and benzyl.
 47. The method of claim38 wherein the effective amount is from about 0.0001 to 10% by weight.48. The method of claim 47 wherein the effective amount is from about0.001 to 5% by weight.
 49. The method of claim 48 wherein the oralcomposition is in the form of a member selected from the groupconsisting of a mouthrinse, a dentifrice, a chewing gum, a lozenge, adispersible oral film, and an oral film forming dentifrice.